The Animal Facility Core (Core A) will meet the special animal needs of the Program Project members. In many cases, the Projects will require double or even triple transgenic/KO mice for the sophisticated experiments outlined in the proposal. The FIRST SPECIFIC AIM of this core is to breed unique and non-routine strains for use by all program project members. Core A will breed mice that are genetically altered in at least two ways (transgenes or knockouts) and genotype them to verify their genetic makeup. The Core will also maintain genetically altered strains used by at least two Projects. In addition, we will use a large number of immunocompomised and autoimmune mice that will require housing in a barrier facility providing a pathogen-free environment, an experienced animal husbandry staff capable of providing quality animal care, and a sophisticated quality assurance program. The availability of quality animals free from adventitious agents is absolutely essential for the success of the research effort proposed in this Program Project Grant. Thus, the SECOND SPECIFIC AIM of this core is to provide a specific pathogen-free environment to maintain mice for the studies proposed in the individual projects. In this regard, the Core will provide additional vigilance and monitoring to ensure that the SPF barrier maintained by the institution is functioning properly. The availability of the core ensures that sufficient mice shared by multiple investigators will be available and the appropriate genetic and health states will be maintained. Finally, the Core will assist investigators in creating bone marrow chimeras and adoptive transferred animals.